PB1809: COMPARISON OF OPTICAL GENOME MAPPING WITH STANDARD OF CARE TESTING TO INVESTIGATE GENOMIC ABNORMALITIES IN HAEMATOLOGICAL MALIGNANCIES: THE EXPERIENCE OF CENTRAL AND SOUTH GENOMIC LABORATORY HUB, UK
Authors: Mariela Muraru, Anna Skowronska, Tyler Wilding, Sara Dyer, Nick Cross, Matthew Salmon, Laura Chiecchio, Andrew Beggs, Joanne Mason
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Here we present the results of Optical Genome Mapping (OGM) validation in West Midlands Regional Genetics Laboratory (WMRGL), UK. OGM a has great potential to become the new gold standard for detecting structural and copy number variations (SVs and CNVs) identified by cytogenetic techniques for routine use in a diagnostic laboratory environment. Our validation cohort consisted of thirty-nine (39) haemato-oncology referrals from two diagnostic laboratories – WMRGL and Wessex Genomics Laboratory Service. Aims: The aim of this study was to evaluate Optical Genome Mapping (OGM) as a potential replacement for aspects of current Standard of Care (SOC) testing in a diagnostic laboratory environment. We show the concordance between OGM and SOC results. Methods: Samples were representative of the types of haematological malignancy referrals routinely received by our laboratories such as Acute Myeloid Leukaemia, Acute Lymphoblastic Leukaemia, Multiple Myeloma, Myelodysplastic Syndrome, Myeloproliferative Disorders and Lymphoproliferative Disorders. Standard of Care (SOC) testing results were available for all analyzed samples based on a combination of G-band metaphase analysis, Fluorescence in Situ Hybridization (FISH) and/or SNP array analysis. Ultra-high molecular weight (UHMW) DNA was isolated from blood, bone marrow, cell pellets and blood cryopreserved specimens, subsequently labelled, and processed for analysis on the Bionano Genomics Saphyr® platform following the manufacturer’s protocols (Bionano Genomics, San Diego, USA). Genome analysis was performed using the Rare Variant Pipeline Analysis on Bionano Access software (v.1.6). Results: Thirty-nine different Haemato-Oncology samples were analyzed. Referral reasons and detailed results of the karyotype, FISH, SNP array and OGM analysis are depicted in Table 1 together with the concordance between the techniques.Table 1. Validation cohort with comparison between the SOC and OGM results. OGM detected most of the structural and copy number abnormalities already reported by SOC testing. As expected, there were some abnormalities missed by OGM due to: abnormalities restricted to dividing cells (samples 43, 50 and 60) whole-arm translocations (sample 73) low coverage by OGM (sample 50) CN-LOH (sample 43) low level disease (samples 23 and 39) Summary/Conclusion: There was high concordance between the results of SOC and OGM testing. Additional aberrations were detected by OGM, some of these with potential clinical relevance. OGM did not detect all abnormalities detected by SOC, but in each case there was a clear explanation. With improvements to capacity of the Saphyr instrument and automation of key processes, we believe that OGM has the potential to replace some SOC testing, including G-band chromosome analysis, currently used in haematological malignancy genomic diagnostics. Keywords: Myeloid malignancies, Lymphoid malignancy, Multiple myeloma, Cytogenetics